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ncRNA
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Insights into Antisense Long Non-Coding RNAs Metabolism and Expression
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Insights into Antisense Long Non-Coding RNAs Metabolism and Expression

A special issue of Non-Coding RNA (ISSN 2311-553X).

Deadline for manuscript submissions: closed (30 September 2022) | Viewed by 20809

Special Issue Editors

Dr. Maxime Wery

E-Mail Website
Guest Editor
Epigenetic and Genome Fluidity, Institut Curie, Sorbonne Université, CNRS UMR 3244, Paris, France
Interests: long non-coding RNA; gene expression; post-transcriptional RNA metabolism; nonsense-mediated mRNA decay; lncRNA-derived micropeptide; functional genomics to ncRNA
Dr. Julien Soudet

E-Mail Website
Guest Editor
Department of Cell Biology, University of Geneva, 1211 Geneva, Switzerland
Interests: non-coding transcription; antisense transcription; chromatin; gene regulation; nucleosomes; nucleosome-depleted regions

Special Issue Information

Dear Colleagues,

While initially considered as pervasive transcripts devoid of any regulatory function, long non-coding (lnc)RNAs have progressively emerged as key players involved in multiple cellular processes.

Among the different classes of lncRNAs, “antisense” (as)lncRNAs are synthesized from the DNA strand opposite to “sense” genes. Over the last few years, they have attracted a lot of attention given their potential to regulate gene expression.

Despite their regulatory importance, aslncRNAs still remain poorly characterized. One reason for this lack of global information on aslncRNAs appears to be their low cellular abundance. In fact, pioneering studies in yeast have highlighted the role of evolutionarily conserved RNA decay machineries in tightly controlling aslncRNAs levels.

In this context, this Special Issue will focus on the expression and the metabolism of aslncRNAs, including antisense transcription, the regulation of aslncRNAs expression and decay, the interactions of aslncRNAs with RNA/DNA, aslncRNAs as regulators of gene expression and other processes, aslncRNAs expression in cancer and diseases, and evolutionary aspects of aslncRNAs.

Manuscripts reporting original research, short communications, methods, and reviews will be considered.

Dr. Maxime Wery
Dr. Julien Soudet
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Non-Coding RNA is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Antisense transcription
  • aslncRNAs expression and decay
  • aslncRNAs metabolism
  • Regulatory aslncRNAs
  • aslncRNAs in cancer and disease

Published Papers (6 papers)

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Research

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17 pages, 3328 KiB  
Article
Epigenetic Regulation of HIV-1 Sense and Antisense Transcription in Response to Latency-Reversing Agents
by Rui Li, Isabella Caico, Ziyan Xu, Mohammad Shameel Iqbal and Fabio Romerio
Non-Coding RNA 2023, 9(1), 5; https://doi.org/10.3390/ncrna9010005 - 10 Jan 2023
Cited by 4 | Viewed by 2352
Abstract
Nucleosomes positioned on the HIV-1 5′ long terminal repeat (LTR) regulate sense transcription as well as the establishment and maintenance of latency. A negative-sense promoter (NSP) in the 3′ LTR expresses antisense transcripts with coding and non-coding activities. Previous studies identified cis-acting [...] Read more.
Nucleosomes positioned on the HIV-1 5′ long terminal repeat (LTR) regulate sense transcription as well as the establishment and maintenance of latency. A negative-sense promoter (NSP) in the 3′ LTR expresses antisense transcripts with coding and non-coding activities. Previous studies identified cis-acting elements that modulate NSP activity. Here, we used the two chronically infected T cell lines, ACH-2 and J1.1, to investigate epigenetic regulation of NSP activity. We found that histones H3 and H4 are present on the 3′ LTR in both cell lines. Following treatment with histone deacetylase inhibitors (HDACi), the levels of H3K27Ac increased and histone occupancy declined. HDACi treatment also led to increased levels of RNA polymerase II (RNPII) at NSP, and antisense transcription was induced with similar kinetics and to a similar extent as 5′ LTR-driven sense transcription. We also detected H3K9me2 and H3K27me3 on NSP, along with the enzymes responsible for these epigenetic marks, namely G9a and EZH2, respectively. Treatment with their respective inhibitors had little or no effect on RNPII occupancy at the two LTRs, but it induced both sense and antisense transcription. Moreover, the increased expression of antisense transcripts in response to treatment with a panel of eleven latency-reversing agents closely paralleled and was often greater than the effect on sense transcripts. Thus, HIV-1 sense and antisense RNA expression are both regulated via acetylation and methylation of lysine 9 and 27 on histone H3. Since HIV-1 antisense transcripts act as non-coding RNAs promoting epigenetic silencing of the 5′ LTR, our results suggest that the limited efficacy of latency-reversing agents in the context of ‘shock and kill’ cure strategies may be due to concurrent induction of antisense transcripts thwarting their effect on sense transcription. Full article
(This article belongs to the Special Issue Insights into Antisense Long Non-Coding RNAs Metabolism and Expression)
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27 pages, 18377 KiB  
Article
Pan-Cancer Analysis Reveals the Prognostic Potential of the THAP9/THAP9-AS1 Sense–Antisense Gene Pair in Human Cancers
by Richa Rashmi and Sharmistha Majumdar
Non-Coding RNA 2022, 8(4), 51; https://doi.org/10.3390/ncrna8040051 - 08 Jul 2022
Cited by 1 | Viewed by 2663
Abstract
Human THAP9, which encodes a domesticated transposase of unknown function, and lncRNA THAP9-AS1 (THAP9-antisense1) are arranged head-to-head on opposite DNA strands, forming a sense and antisense gene pair. We predict that there is a bidirectional promoter that potentially regulates the expression of THAP9 [...] Read more.
Human THAP9, which encodes a domesticated transposase of unknown function, and lncRNA THAP9-AS1 (THAP9-antisense1) are arranged head-to-head on opposite DNA strands, forming a sense and antisense gene pair. We predict that there is a bidirectional promoter that potentially regulates the expression of THAP9 and THAP9-AS1. Although both THAP9 and THAP9-AS1 are reported to be involved in various cancers, their correlative roles on each other’s expression has not been explored. We analyzed the expression levels, prognosis, and predicted biological functions of the two genes across different cancer datasets (TCGA, GTEx). We observed that although the expression levels of the two genes, THAP9 and THAP9-AS1, varied in different tumors, the expression of the gene pair was strongly correlated with patient prognosis; higher expression of the gene pair was usually linked to poor overall and disease-free survival. Thus, THAP9 and THAP9-AS1 may serve as potential clinical biomarkers of tumor prognosis. Further, we performed a gene co-expression analysis (using WGCNA) followed by a differential gene correlation analysis (DGCA) across 22 cancers to identify genes that share the expression pattern of THAP9 and THAP9-AS1. Interestingly, in both normal and cancer samples, THAP9 and THAP9-AS1 often co-express; moreover, their expression is positively correlated in each cancer type, suggesting the coordinated regulation of this H2H gene pair. Full article
(This article belongs to the Special Issue Insights into Antisense Long Non-Coding RNAs Metabolism and Expression)
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18 pages, 2492 KiB  
Article
Interdependent Transcription of a Natural Sense/Antisense Transcripts Pair (SLC34A1/PFN3)
by Hany S. Zinad, Chanachai Sae-Lee, Maria Ascensión Ariza-Mateos, Grace Adamson, Mushtaq Mufleh Khazeem, Amber Knox, Git Chung, Jelena Mann and Andreas Werner
Non-Coding RNA 2022, 8(1), 19; https://doi.org/10.3390/ncrna8010019 - 11 Feb 2022
Cited by 2 | Viewed by 3267
Abstract
Natural antisense transcripts (NATs) constitute a significant group of regulatory, long noncoding RNAs. They are prominently expressed in testis but are also detectable in other organs. NATs are transcribed at low levels and co-expressed with related protein coding sense transcripts. Nowadays NATs are [...] Read more.
Natural antisense transcripts (NATs) constitute a significant group of regulatory, long noncoding RNAs. They are prominently expressed in testis but are also detectable in other organs. NATs are transcribed at low levels and co-expressed with related protein coding sense transcripts. Nowadays NATs are generally considered as regulatory, long noncoding RNAs without closer focus on the inevitable interference between sense and antisense expression. This work describes a cellular system where sense and antisense transcription of a specific locus (SLC34A1/PFN3) is induced using epigenetic modifiers and CRISPR-Cas9. The renal cell lines HEK293 and HKC-8 do not express SLC34A1/PFN3 under normal culture conditions. Five-day exposure to dexamethasone significantly stimulates sense transcript (SLC34A1) levels and antisense (PFN3) minimally; the effect is only seen in HEK293 cells. Enhanced expression is paralleled by reduced sense promoter methylation and an increase in activating histone marks. Expression is further modulated by cassettes that stimulate the expression of sense or antisense transcript but disrupt protein coding potential. Constitutive expression of a 5′-truncated SLC34A1 transcript increases sense expression independent of dexamethasone induction but also stimulates antisense expression. Concordant expression is confirmed with the antisense knock-in that also enhances sense expression. The antisense effect acts on transcription in cis since transient transfection with sense or antisense constructs fails to stimulate the expression of the opposite transcript. These results suggest that bi-directional transcription of the SLC34A1/PFN3 locus has a stimulatory influence on the expression of the opposite transcript involving epigenetic changes of the promoters. In perspective of extensive, previous research into bi-directionally transcribed SLC34A loci, the findings underpin a hypothesis where NATs display different biological roles in soma and germ cells. Accordingly, we propose that in somatic cells, NATs act like lncRNAs–with the benefit of close proximity to a potential target gene. In germ cells, however, recent evidence suggests different biological roles for NATs that require RNA complementarity and double-stranded RNA formation. Full article
(This article belongs to the Special Issue Insights into Antisense Long Non-Coding RNAs Metabolism and Expression)
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Review

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10 pages, 941 KiB  
Review
RNA-Mediated Regulation of Meiosis in Budding Yeast
by Vidya Vardhini Pondugala and Krishnaveni Mishra
Non-Coding RNA 2022, 8(6), 77; https://doi.org/10.3390/ncrna8060077 - 15 Nov 2022
Cited by 1 | Viewed by 2208
Abstract
Cells change their physiological state in response to environmental cues. In the absence of nutrients, unicellular fungi such as budding yeast exit mitotic proliferation and enter the meiotic cycle, leading to the production of haploid cells that are encased within spore walls. These [...] Read more.
Cells change their physiological state in response to environmental cues. In the absence of nutrients, unicellular fungi such as budding yeast exit mitotic proliferation and enter the meiotic cycle, leading to the production of haploid cells that are encased within spore walls. These cell state transitions are orchestrated in a developmentally coordinated manner. Execution of the meiotic cell cycle program in budding yeast, Saccharomyces cerevisiae, is regulated by the key transcription factor, Ime1. Recent developments have uncovered the role of non-coding RNA in the regulation of Ime1 and meiosis. In this review, we summarize the role of ncRNA-mediated and RNA homeostasis-based processes in the regulation of meiosis in Saccharomyces cerevisiae. Full article
(This article belongs to the Special Issue Insights into Antisense Long Non-Coding RNAs Metabolism and Expression)
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16 pages, 6947 KiB  
Review
Navigating the Multiverse of Antisense RNAs: The Transcription- and RNA-Dependent Dimension
by Giulia Pagani, Cecilia Pandini and Paolo Gandellini
Non-Coding RNA 2022, 8(6), 74; https://doi.org/10.3390/ncrna8060074 - 26 Oct 2022
Cited by 6 | Viewed by 2392
Abstract
Evidence accumulated over the past decades shows that the number of identified antisense transcripts is continuously increasing, promoting them from transcriptional noise to real genes with specific functions. Indeed, recent studies have begun to unravel the complexity of the antisense RNA (asRNA) world, [...] Read more.
Evidence accumulated over the past decades shows that the number of identified antisense transcripts is continuously increasing, promoting them from transcriptional noise to real genes with specific functions. Indeed, recent studies have begun to unravel the complexity of the antisense RNA (asRNA) world, starting from the multidimensional mechanisms that they can exert in physiological and pathological conditions. In this review, we discuss the multiverse of the molecular functions of asRNAs, describing their action through transcription-dependent and RNA-dependent mechanisms. Then, we report the workflow and methodologies to study and functionally characterize single asRNA candidates. Full article
(This article belongs to the Special Issue Insights into Antisense Long Non-Coding RNAs Metabolism and Expression)
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17 pages, 1104 KiB  
Review
From Yeast to Mammals, the Nonsense-Mediated mRNA Decay as a Master Regulator of Long Non-Coding RNAs Functional Trajectory
by Sara Andjus, Antonin Morillon and Maxime Wery
Non-Coding RNA 2021, 7(3), 44; https://doi.org/10.3390/ncrna7030044 - 27 Jul 2021
Cited by 10 | Viewed by 5910
Abstract
The Nonsense-Mediated mRNA Decay (NMD) has been classically viewed as a translation-dependent RNA surveillance pathway degrading aberrant mRNAs containing premature stop codons. However, it is now clear that mRNA quality control represents only one face of the multiple functions of NMD. Indeed, NMD [...] Read more.
The Nonsense-Mediated mRNA Decay (NMD) has been classically viewed as a translation-dependent RNA surveillance pathway degrading aberrant mRNAs containing premature stop codons. However, it is now clear that mRNA quality control represents only one face of the multiple functions of NMD. Indeed, NMD also regulates the physiological expression of normal mRNAs, and more surprisingly, of long non-coding (lnc)RNAs. Here, we review the different mechanisms of NMD activation in yeast and mammals, and we discuss the molecular bases of the NMD sensitivity of lncRNAs, considering the functional roles of NMD and of translation in the metabolism of these transcripts. In this regard, we describe several examples of functional micropeptides produced from lncRNAs. We propose that translation and NMD provide potent means to regulate the expression of lncRNAs, which might be critical for the cell to respond to environmental changes. Full article
(This article belongs to the Special Issue Insights into Antisense Long Non-Coding RNAs Metabolism and Expression)
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